Conductive Hydrogels for Exogenous Sensing and Cell Fate Control.

Next generation technologies linking living systems to computers will require materials built on biology, an approach that may address persistent challenges in stable and multimodal information exchange. Here, we present a semi-synthetic hydrogel, designed to emulate key features of native extracellular matrix (ECM) while offering electrically tunable functionality. We engineer interactions between sulfated glycosaminoglycans (sGAGs) and a semiconducting organic polymer (poly(3,4-ethylenedioxythiophene), PEDOT) within a soft hydrogel network (PEDOT:sGAGh). We demonstrate control over the material's nanoarchitecture, electrochemical behavior, and biomolecular interactions. In particular, PEDOT:sGAGh exhibits affinity for bioactive proteins, including growth factors, and allows their release or retention to be modulated by low-voltage stimulation. This enables electrical control over macromolecular cues for cell differentiation, a capability not found in natural ECM or conventional conductive hydrogels. These functions are achieved with ultra-low PEDOT content (≈1 wt.%), preserving the hydrogel's tissue-like softness and high water content. The PEDOT:sGAGh material can be integrated as a bioactive coating on electrodes, or into 3D organic electrochemical transistors (OECTs). Our results position PEDOT:sGAGh as a versatile platform for realizing biohybrid circuits that bridge molecular signaling and solid-state electronics, thus paving the way for brain-machine interfaces that operate beyond purely electrical modes of interaction.